Nearly one trillion bacteria reside in our gut, but amazingly, our immune system does not wage a war against them. How is such a peaceful coexistence achieved? There is likely a battery of mechanisms; however, one is necessary to keep the bacteria in the small intestine and colon physically separated from the immunologically active mucosal epithelium. Vaishnava et al. (see the Perspective by Johansson and Hansson) used a combination of genetic approaches to demonstrate that signaling downstream of Toll-like receptors (TLRs), which recognize conserved signatures of microorganisms to initiate immune responses, is required to maintain this separation.